Genome-Wide Placental Gene Methylations in Gestational Diabetes Mellitus, Fetal Growth and Metabolic Health Biomarkers in Cord Blood

作者：Wen-Juan Wang, Rong Huang, Tao Zheng, Qinwen Du, Mengnan Yang, Yajie Xu, Xin Liu, Minyi Tao, Hua He, Fang Fang, Fēi Li, Jian‐Gao Fan, Jun Zhang, Laurent Briollais, Fengxiu Ouyang, Zhong‐Cheng Luo · 发表于：Frontiers in Endocrinology · 年份：2022 · DOI：10.3389/fendo.2022.875180 · 被引用次数：35 · 研究领域：Gestational Diabetes Research and Management、Pregnancy and preeclampsia studies、Epigenetics and DNA Methylation

Gestational diabetes mellitus (GDM) "program" an elevated risk of metabolic syndrome in the offspring. Epigenetic alterations are a suspected mechanism. GDM has been associated with placental DNA methylation changes in some epigenome-wide association studies. It remains unclear which genes or pathways are affected, and whether any placental differential gene methylations are correlated to fetal growth or circulating metabolic health biomarkers. In an epigenome-wide association study using the Infinium MethylationEPIC Beadchip, we sought to identify genome-wide placental differentially methylated genes and enriched pathways in GDM, and to assess the correlations with fetal growth and metabolic health biomarkers in cord blood. The study samples were 30 pairs of term placentas in GDM vs. euglycemic pregnancies (controls) matched by infant sex and gestational age at delivery in the Shanghai Birth Cohort. Cord blood metabolic health biomarkers included insulin, C-peptide, proinsulin, IGF-I, IGF-II, leptin and adiponectin. Adjusting for maternal age, pre-pregnancy BMI, parity, mode of delivery and placental cell type heterogeneity, 256 differentially methylated positions (DMPs,130 hypermethylated and 126 hypomethylated) were detected between GDM and control groups accounting for multiple tests with false discovery rate <0.05 and beta-value difference >0.05. WSCD2 was identified as a differentially methylated gene in both site- and region-level analyses. We validated 7 hypermethylat...